Response to respiratory syncytial (RS) virus differs from the response to most viruses in 2 important ways. 1. The severe bronchiolitis it causes occurs chiefly during the first 6 months of life, when most infants have protection against most of the usual childhood viral diseases. 2. Killed-virus vaccines, which fail to protect older infants, apparently also sensitize some vaccinees; they develop the severe disease ordinarily limited to young infants. These peculiar responses may be related to characteritics of the virus about which little is known: its structure, replication and/or maturation, effect on host cells, or some combination of these, such as nonreleased virus, interacting with the patient's immune responses. Therefore, we propose to study the virion, its replication and effect on host cells. We have purified the virus, resolved its proteins into 6-8 polypeptides, and sequentially, separated these from the virion, making possible the first comparison between the structural polypeptides of RS and their organization, and those of other RNA enveloped viruses. We have also established a persistent RS virus infection in HeLa cells. Described are proposed experiments to: 1. determine whether each polypeptide is a separate gene product, 2. isolate and size the nucleic acid of purified virus, 3. continue studying the effect of infection on host-cell synthesis, 4. determine when and where nucleocapsid and envelope proteins are synthesized, and the kinetics of their association with plasma membrane and incorporation into virions, and 5. characterize the virus-cell interaction in the persistently infected culture. These studies will also: 1. determine whether any viral polypeptides, especially the glycoproteins, are derived from larger, precursor proteins, and whether polypeptide processing has special aspects indicating why 90% of the virions are not released after budding, 2. provide the basis for rational classification of the virus, and 3. provide insight into the factors involved in pathogenesis, in both cell culture and lower respiratory disease.